Regulation of 3β-Hydroxysteroid Dehydrogenase/∆5-∆4 Isomerase: A Review

This review focuses on the expression and regulation of 3β-hydroxysteroi ddehydrogenase/Δ5-Δ4 isomerase (3β-HSD), with emphasis on the porcine version. 3β-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based on currently available literature covering humans,rodents and pigs, this review provides an overview of the present knowledge concerning the regulatory mechanisms for 3β-HSD at all omic levels. The HSD isoenzymes are essential in steroid hormone metabolism, both in the synthesis and degradation of steroids. They display tissue-specific expression and factors influencing their activity, which therefore indicates their tissue-specific responses. 3β-HSD is involved in the synthesis of a number of natural steroid hormones, including progesterone and testosterone, and the hepatic degradation of the pheromone androstenone. In general, a number of signaling and regulatory pathways have been demonstrated to influence 3β-HSD transcription and activity, e.g., JAK-STAT, LH/hCG, ERα, AR, SF-1 and PPARα. The expression and enzymic activity of 3β-HSD are also influenced by external factors, such as dietary composition. Much of the research conducted on porcine 3β-HSD is motivated by its importance for the occurrence of the boar taint phenomenon that results from high concentrations of steroids such as androstenone. This topic is also examined in this review

The "ram effect": new insights into neural modulation of the gonadotropic axis by male odors and socio-sexual interactions

Reproduction in mammals is controlled by the hypothalamo-pituitary-gonadal (HPG) axis under the influence of external and internal factors such as photoperiod, stress, nutrition, and social interactions. Sheep are seasonal breeders and stop mating when day length is increasing (anestrus). However, interactions with a sexually active ram during this period can override the steroid negative feedback responsible for the anoestrus state, stimulate LH secretion and eventually reinstate cyclicity. This is known as the ram effect and research into the mechanisms underlying it is shedding new light on HPG axis regulation. The first step in the ram effect is increased LH pulsatile secretion in anestrus ewes exposed to a sexually active male or only to its fleece, the latter finding indicating a pheromone-like effect. Estradiol secretion increases in all ewes and this eventually induces a LH surge and ovulation, just as during the breeding season. An exception is a minority of ewes that exhibit a precocious LH surge (within 4h) with no prior increase in estradiol. The main olfactory system and the cortical nucleus of the amygdala are critical brain structures in mediating the ram effect since it is blocked by their inactivation. Sexual experience is also important since activation (increased c-fos expression) in these and other regions is greatly reduced in sexually naïve ewes. In adult ewes kisspeptin neurons in both arcuate and preoptic regions and some preoptic GnRH neurons are activated 2h after exposure to a ram. Exposure to rams also activates noradrenergic neurons in the locus coeruleus and A1 nucleus and increased noradrenalin release occurs in the posterior preoptic area. Pharmacological modulation of this system modifies LH secretion in response to the male or his odor. Together these results show that the ram effect can be a fruitful model to promote both a better understanding of the neural and hormonal regulation of the HPG axis in general and also the spe

Stimulatory Effects of Estradiol on Lh Secretion During the Estrous Cycle of the Ewe (Progesterone, Lh Surge).

Estradiol is known to have both stimulatory and inhibitory effects on LH secretion by the ewe. The importance of the former in orchestrating the hormonal events of the follicular phase of the ovine estrous cycle was investigated. In the first study, estradiol was shown to be capable of stimulating LH-pulse frequency in long-term castrated ewes. An experimental model was then developed in which endogenous GnRH ecretion in the ewe was abolished while pituitary responsiveness to oxogenous GnRH was not significantly altered (Progesterone Suppressed Model; PSM). This model, consisting of ovariectomy and treatment with progesterone during anestrus, was applied to the study of the inverse relationship between frequency and amplitude of LH-pulses. The results showed that GnRH-pulse frequency can affect pituitary responsiveness to GnRH and thus account for the inverse relationship. LH-surge responses were induced in the PSM by simulation of the pituitary with estradiol and GnRH treatments thus demonstrating that the blockade of the LH surge by progesterone is affected at a neural rather than an hypophyseal level. Further investigation showed that gradual increases in GnRH-pulse frequency were ineffective in producing gonadotropin surges whereas abrupt increases to the same end-point were effective. This suggested that an abrupt increase in GnRH stimulation of the pituitary is needed to induce the surge; a further study showed that attainment of peak follicular phase estradiol concentrations is also required. These observations are consistent with the hypothesis that, prior to the surge, a positive feedback relationship between estradiol and LH allows development and maturation of the ovarian follicles. High levels of estradiol present late in the follicular phase then affect neural and hypophyseal function to produce the LH surge.Ph.D.Animal PhysiologyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/161261/1/8702758.pd